#oxidative stress

Teratogens

Alcohol-induced superoxide radicals cause:

Embryos possess immature antioxidant defense systems with low catalase and superoxide dismutase activity. Ethanol oxidation by cytochrome P450 2E1 generates superoxide anion, hydrogen peroxide and hydroxyl radicals causing lipid peroxidation and mitochondrial permeability transition. Elevated ROS activates stress kinases JNK and p53 inducing intrinsic apoptosis pathway via Bax and cytochrome c release leading to caspase-mediated cell death in neural crest and neural tube. Antioxidant treatment reduces fetal alcohol defects in animal models. Cell death rather than increased proliferation underl

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Alcohol superoxide radicals cause cell death.

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Cell Organelles

The major function of peroxisomes is:

Peroxisomes are single membrane oxidative organelles discovered by Rhodin and De Duve, numbering hundreds per cell, containing more than fifty enzymes producing and degrading hydrogen peroxide. Beta-oxidation of very long chain fatty acids greater than twenty two carbons, branched phytanic acid alpha-oxidation, bile acid intermediate shortening and ether lipid synthesis of plasmalogens providing antioxidant membranes and myelin components occur via enzymes acyl-CoA oxidase generating H2O2, bifunctional enzyme and thiolase. Catalase converts two H2O2 to water and oxygen detoxifying, also urate

Ref: Wanders Annu Rev Biochem; peroxisome beta-oxidation VLCFA catalase PTS1 PTS2 Pex import.

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Microbial Physiology

What is the role of superoxide dismutase in aerobic bacteria?

Superoxide radical generated when flavoenzymes and respiratory chain components univalently reduce oxygen, highly toxic inactivating dehydratases bearing exposed iron sulfur clusters like aconitase and fumarase releasing free iron that fuels Fenton chemistry producing hydroxyl radical. Superoxide dismutase constitutes primary defense dismutating two superoxides into dioxygen and hydrogen peroxide reaction two O2 superoxide plus two protons to O2 plus H2O2. Enzymes classified by metal cofactor manganese SodA inducible by SoxRS, iron SodB constitutive, copper zinc SodC periplasmic exported via S

Ref: Brock Biology of Microorganisms, 16th ed., Chapter 6: Superoxide dismutase - ROS detoxification.

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Microbial Physiology

Reactive oxygen species (ROS) are detoxified by:

Aerobic respiration inherently leaks electrons to oxygen at Complex I and Complex II producing superoxide anion which dismutates to hydrogen peroxide and can generate highly destructive hydroxyl radical via Haber-Weiss and Fenton chemistry catalyzed by iron. These reactive oxygen species damage virtually all macromolecules including proteins forming carbonyls, lipids forming peroxides and DNA forming 8-oxoguanine leading to mutations. Bacteria deploy multilayered detoxification network. Superoxide dismutase encoded by sodA manganese cofactored, sodB iron cofactored and sodC copper-zinc peripla

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: Catalase and Superoxide Dismutase in ROS Detoxification.

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Microbial Physiology

Which bacterial enzyme neutralizes hydrogen peroxide?

Hydrogen peroxide is unavoidable byproduct of flavoprotein oxidases such as NADH oxidase and autoxidation of menaquinones generating reactive oxygen stress capable of hydroxyl radical formation via Fenton reaction damaging iron-sulfur clusters and DNA. Aerobic bacteria depend on extremely efficient enzymatic detoxification. Catalase is tetrameric heme enzyme containing heme b active site where first H2O2 oxidizes ferric heme to Compound I ferryl oxo porphyrin radical, second H2O2 reduces Compound I releasing water and dioxygen. Catalytic rate is among highest known about ten million molecules

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: Catalase Function and Hydrogen Peroxide Neutralization.

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Microbial Physiology

Which molecule acts as an electron donor in bacterial oxidative stress response?

Redox homeostasis during oxidative stress requires continuous electron flow from reduced pyridine nucleotide NADPH generated by pentose phosphate pathway to thiol antioxidant enzymes. Thioredoxin is small 12 kDa dithiol protein with highly conserved WCGPC active motif forming reversible intramolecular disulfide acting as mobile electron shuttle. Reduced thioredoxin provides low-potential electrons directly to peroxiredoxins such as AhpC and Tpx that reduce hydrogen peroxide and organic peroxides to water and alcohols, to methionine sulfoxide reductases MsrA and MsrB that repair oxidized methio

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 7: Thioredoxin as Electron Donor in Oxidative Defense.

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Microbial Physiology

Which enzyme neutralizes hydrogen peroxide (H₂O₂) in bacterial cells?

Hydrogen peroxide at even low micromolar concentrations of 1 to 2 micromolar causes inactivation of mononuclear iron enzymes and iron-sulfur dehydratases such as fumarase via Fenton chemistry generating highly reactive hydroxyl radicals that oxidize DNA generating 8-oxoguanine and protein carbonyls leading to mutagenesis. Bacteria deploy specialized scavenging enzymes for peroxide detoxification. Catalases are predominantly heme-containing tetrameric enzymes containing protoheme IX or heme b in each active site that dismutate two molecules of H2O2 into water and molecular oxygen with extremely

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: Catalase and Hydrogen Peroxide Detoxification.

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Microbial Physiology

The primary function of glutathione in bacterial stress response is:

Glutathione is a low-molecular-weight tripeptide gamma-glutamyl-cysteinyl-glycine present at millimolar concentrations up to 10 mM in many Gram-negative bacteria such as Escherichia coli and few Gram-positives that synthesize it via GshA and GshB. Reduced form GSH serves as major thiol buffer and electron donor protecting against reactive oxygen species generated continuously by endogenous respiratory electron transport and by host immune oxidative burst involving NADPH oxidase-dependent production of superoxide during phagocytosis. It directly scavenges superoxide anion, hydroxyl radical and

Ref: Prescott's Microbiology, 11th ed., Chapter 7: Glutathione and Oxidative Stress Protection in Bacteria.

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Microbial Physiology

The Thioredoxin system in bacteria is essential for:

Maintenance of intracellular reducing environment and proper thiol-disulfide balance is crucial for protein function, enzyme activity and protection against oxidative damage that would otherwise cause aggregation. The thioredoxin system consists of small 12 kDa redox-active protein thioredoxin TrxA with highly conserved active site motif WCGPC containing two cysteines, flavoprotein thioredoxin reductase TrxB that transfers electrons from NADPH to oxidized thioredoxin via FAD and target disulfide-containing proteins. During oxidative stress or normal oxidative protein maturation in periplasm, i

Ref: Lodish et al., Molecular Cell Biology, 8th ed., Chapter 21: Thioredoxin System and Disulfide Bond Reduction.

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Microbial Physiology

PerR, OxyR, and SoxR regulate bacterial responses to:

Aerobic metabolism inevitably generates reactive oxygen species including superoxide radical anion and hydrogen peroxide via single-electron leakage from respiratory flavoproteins and autoxidation of reduced ferredoxins that damage solvent-exposed iron-sulfur clusters, DNA bases and unsaturated lipids. Bacteria have evolved exquisite sensing transcription factors that regulate defensive regulons. OxyR in Escherichia coli contains highly reactive cysteines C199 and C208 that when oxidized by low micromolar H2O2 form a reversible intramolecular disulfide bond driving conformational change to act

Ref: Storz and Imlay, Oxidative Stress Regulators, Annu Rev Microbiol: OxyR, PerR, SoxR Oxidative Stress Systems.

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